Anti-Tribbles Homo log 2 (TRIB2) Autoantibodies in Narcolepsy are Associated with Recent Onset of Cataplexy

被引:99
作者
Kawashima, Minae [1 ]
Lin, Ling [1 ]
Tanaka, Susumu [2 ]
Jennum, Poul [3 ]
Knudsen, Stine [3 ]
Nevsimalova, Sona [4 ,5 ]
Plazzi, Giuseppe [6 ]
Mignot, Emmanuel [1 ]
机构
[1] Stanford Univ, Sch Med, Ctr Narcolepsy, Palo Alto, CA 94304 USA
[2] Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Sleep Disorders Res Project, Tokyo, Japan
[3] Univ Copenhagen, Glostrup Hosp, Danish Ctr Sleep Med, Glostrup, Denmark
[4] Charles Univ Prague, Fac Med 1, Dept Neurol, Prague, Czech Republic
[5] Gen Teaching Hosp, Prague, Czech Republic
[6] Univ Bologna, Dept Neurol Sci, Sleep Disorders Ctr, Bologna, Italy
关键词
Human narcolepsy; Tribbles homolog 2 (TRIB2); autoantibody; anti-streptolysin O (ASO); HYPOCRETIN OREXIN; ANTIBODIES; DIAGNOSIS; SLEEP; MUTATION; UVEITIS; ASSAY;
D O I
10.1093/sleep/33.7.869
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Study Objective: Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases. Participants and Methods: Participants included (1) 90 cases with cataplexy, (2) 57 cases without cataplexy, and (3) 156 age-sex matched controls, including 73 human leukocyte antigen (HLA)-DQB1*0602 allele carriers. A radioligand binding assay was used to detect anti-TRIB2 antibodies. Results: Anti-TRIB2 antibodies were prevalent in HLA-DQB1*0602 positive cases with cataplexy (25.0% of 76) and rare in cases without cataplexy (3.5% of 57, OR = 9.2, 95% CI = 2.5 - 33.5, P = 6.0 x 10(-4)) or controls (4.5% of 156, OR = 7.1, 95% CI = 3.1 - 16.2, P = 9.3 x 10(-6)). Anti-TRIB2 positivity in controls was not associated with DQB1*0602. In DQB1*0602 narcolepsy-cataplexy cases, the presence of anti-TRIB2 was associated with short disease duration (2.3 years from cataplexy onset), with 41.0% positive in this group (OR = 7.4 versus cases with onset > 2.3 years, 95% CI = 1.9 - 28.5, P = 9.0 x 10(-4)). Anti-TRIB2 positivity in 39 DQB1*0602 positive recent onset cases was associated with increased ASO antibody (> 200 IU) (OR = 6.2, 95% CI = 1.6 - 24.6, P = 0.01), but did not correlate with age, gender, or body mass index. Conclusion: Anti-TRIB2 autoantibodies are strongly associated with narcolepsy close to cataplexy onset (<= 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.
引用
收藏
页码:869 / 874
页数:6
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